Molecular Similarity Determination of Heteroaromatic Ring Fragments Using GRID and Multivariate Data Analysis
Thierry Langer · Quantitative Structure-Activity Relationships · 1996
Abstract This study reports on molecular similarity determination for heteroaromatic ring fragments permitting to take into account differences in anchoring positions of such substructures in a given molecule. A total of 72 aromatic moieties (five‐ and six‐membered monocyclic and fused benzoannelated heteroaromatics containing one or two heteroatoms) was characterized by interaction energy calculations using a total of 6 multi atom probes within the GRID program and new QSAR descriptors were generated from principal component analysis of the interaction energy matrices thus obtained. A hierarchical clustering procedure of the obtained principal components as well as applying factorial design criteria allowed partitioning of the heteroaromatic substituents into similar families and permitted a classification of structures according to their molecular similarity. The descriptors now obtained were tested for their prediction capacity using different previously reported datasets of biologically active compounds. The results obtained hereby clearly demonstrate the usefulness of 3D derived descriptors.